Pharmaceutical Chemistry (Theses and Dissertations)http://hdl.handle.net/2262/199
Pharmaceutical Chemistry (Theses and Dissertations)Tue, 22 Jan 2019 00:46:42 GMT2019-01-22T00:46:42ZStability and hydrolysis studies of novel dual acting conjugate drugs with anitcancer activityhttp://hdl.handle.net/2262/78256
Stability and hydrolysis studies of novel dual acting conjugate drugs with anitcancer activity
Yassin, Bassem I.
Tamoxifen is currently a first-line endocrine therapy for the adjuvant treatment of Estrogen Receptor (ER) positive breast cancer. The antiestrogenic properties of this compound are related to its ability to compete for estrogen binding sites in target tissues such as the breast and bone. In this research project carried in the Pharmaceutical Chemistry research laboratory in the School of Pharmacy and Pharmaceutical Sciences, a novel series of estrogen receptor modulators was developed. Some of these compounds prevent estrogen binding to its receptor with a higher potency than Tamoxifen, while also inhibiting the proliferation of a human MCF- 7 breast carcinoma cell line. In this study the physiochemical properties and specific structural requirements of drug-like molecules for optimum estrogen receptor binding are examined. The stability of these ligands which are active at the estrogen receptor are specifically investigated.The study of novel potent drug candidates coupled with the elucidation of the mode of action will advance our understanding of and ability to combat hormone dependent breast cancer. The design, synthesis, biochemistry and stability of dual acting estrogen receptor conjugates are now investigated.
Sat, 01 Jan 2011 00:00:00 GMThttp://hdl.handle.net/2262/782562011-01-01T00:00:00ZInvestigations of beta-lactams as novel bioactive compoundshttp://hdl.handle.net/2262/78246
Investigations of beta-lactams as novel bioactive compounds
Wang, Shu
A natural stilbene product combretastatin A-4 (CA-4) is a known anti-cancer compound, which exerts its mechanism of action at the colchicine binding site on tubulin, a protein that is essential for the replication of cells. The synthesis and study of structure-activity relationships of a series of CA-4 analogues are described in which the four-member β-lactam heterocycle (azetidin-2-one) ring scaffold replaces the cis double bond in combretastatin A-4. A library of β-lactam compounds (CA-4 analogues) which are mimics of the substituted aryl ‘A’ ring and ‘B’ ring of CA-4 was synthesised using both Staudinger and Reformatsky reactions. Additional β-lactam compounds were prepared with diverse C-3 substitution at the β-lactam ring by Heck reaction, Diels-Alder reaction, aldol type reaction, alkylation and epoxidation reactions. A series of phosphate ester prodrugs and amino acid prodrugs were synthesised by suitable coupling reactions to improve the stability and solubility of the most active compounds.
Tue, 01 Jan 2013 00:00:00 GMThttp://hdl.handle.net/2262/782462013-01-01T00:00:00ZThe design, synthesis and biological evaluation of novel barbiturate-based MMP inhibitorshttp://hdl.handle.net/2262/78245
The design, synthesis and biological evaluation of novel barbiturate-based MMP inhibitors
Wang, Jun
Matrix metalloproteinases (MMPs) are a group of Zn-dependent endopeptidases that participate in many diseases. Two MMPs, MMP-2 and MMP-9, which are especially associated with inflammatory diseases and tumor metastasis have been considered as promising target for arthritis, stroke, IBD, various pulmonary disorders and cancer. A great number of MMP inhibitors have been reported and are classified into different groups based on their structure, including hydroxamates, carboxylates, and thiols. Although some of these compounds exhibit great potency on inhibition of MMPs, their clinical trial results are disappointed due to lack of selectivity. Recently, appropriate C-5 substituted barbiturates have been found to show MMP inhibitory effects. Since barbiturates have been used as sedatives and hypnotics for decades and have well established clinical history, the MMP inhibitors we prepared were based on the structure of barbiturate.
Fri, 01 Jan 2010 00:00:00 GMThttp://hdl.handle.net/2262/782452010-01-01T00:00:00ZFlexible estrogen receptor modulatorshttp://hdl.handle.net/2262/78212
Flexible estrogen receptor modulators
Smith, Helena M.
Tamoxifen is a selective estrogen receptor modulator (SERM) with a triarylethylene structure, which has estrogenic activity in bone and endometrial tissue, yet antagonises the actions of estrogen in other tissues including breast tissue. It was proposed in the present work to develop novel diaryl and triaryl analogues with a preferable, more selective activity profile than that of tamoxifen. This thesis is presented in three different sections. The first section covers the synthesis of a number of novel, flexible and non-fiexible analogues closely related to the anti-estrogen tamoxifen. The second section includes the synthesis of dihydrochalcones and subsequently, from these, the preparation of numerous highly flexible tamoxifen analogues. The structures of these products were verified using the following; TLC analysis, melting points, 1H NMR, 13C NMR, F19 NMR, and Infra-red spectrometry and Mass spectrometry.
Sat, 01 Jan 2005 00:00:00 GMThttp://hdl.handle.net/2262/782122005-01-01T00:00:00Z